Tetrahydrocannabinol

Pharmacology & Research

Tetrahydrocannabinol is the main psychoactive constituent of cannabis and the reason the plant is intoxicating. Unlike CBD, it acts directly on the endocannabinoid receptors — a partial agonist at both CB1 (concentrated in the brain, behind the effects on mood, perception, appetite and memory) and CB2 (in immune tissue). That direct CB1 action is a double edge: it powers THC’s genuine medicinal uses — antinausea, appetite stimulation, analgesia — and also its psychoactivity, impairment and dependence liability. Its best clinical evidence comes from standardised pharmaceutical forms: synthetic THC (dronabinol, nabilone) as an antiemetic, and a standardised 1:1 THC:CBD spray (nabiximols) for multiple-sclerosis spasticity ^{1,2,3Reference 1Smith LA et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →Reference 2Wade DT et al. · 2010Meta-analysisMeta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosisView study →Reference 3Filippini G et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →}.

0. Evidence by application

Support is an experimental score — a composite weighted by study type (human > animal > in vitro) and volume, tempered for isolate-vs-plant match. A beta, not a validated metric. Each application links to its write-up.

Application	Support	Rests on
MS spasticity	████████░░ 78%	RCTs & meta-analyses of nabiximols (standardised THC:CBD); approved in many countries 2,3Reference 2Wade DT et al. · 2010Meta-analysisMeta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosisView study →Reference 3Filippini G et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →
Chemotherapy nausea	███████░░░ 70%	Licensed synthetic THC (dronabinol/nabilone); Cochrane-reviewed, older trials 1Reference 1Smith LA et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →
Chronic & neuropathic pain	███████░░░ 66%	Many RCTs; small effect; cancer pain largely null 5,6Reference 5Whiting PF et al. · 2015Meta-analysisCannabinoids for Medical Use: A Systematic Review and Meta-analysisView study →Reference 62026Systematic reviewCannabis-based medicines for chronic neuropathic pain in adults — Cochrane systematic reviewView study →
Appetite & cachexia	████░░░░░░ 42%	CB1 mechanism real; cancer-cachexia trials largely null 4Reference 4Mücke M et al. · 2018Meta-analysisSystematic review and meta-analysis of cannabinoids in palliative medicineView study →
Glaucoma	███░░░░░░░ 30%	Lowers eye pressure but only ~3–4 h — not practical 8Reference 8Tomida I et al. · 2004ReviewCannabinoids and glaucoma — reviewView study →

1. MS spasticity

Nabiximols — a standardised 1:1 THC:CBD oromucosal spray — is licensed in many countries for multiple-sclerosis spasticity that resists first-line drugs. A meta-analysis of the pivotal RCTs found a modest but reproducible reduction in patient-rated spasticity ^{2Reference 2Wade DT et al. · 2010Meta-analysisMeta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosisView study →}, and the 2022 Cochrane review rates the evidence low-to-moderate certainty with a small average effect ^{3Reference 3Filippini G et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →}.

Gap: the effect is modest and driven partly by subjective self-report; roughly half of patients are non-responders, and the standardised spray doesn’t represent smoked or edible cannabis ^{3Reference 3Filippini G et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →}.

2. Chemotherapy nausea

Synthetic THC (dronabinol, nabilone) has been a licensed antiemetic since the 1980s — one of cannabis’s oldest evidence-based uses. A Cochrane review found cannabinoids more effective than placebo and broadly comparable to older antiemetics, and often the treatment patients preferred ^{1Reference 1Smith LA et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →}.

Gap: the trials predate modern antiemetics; benefit over today’s standard drugs (setrons, NK1 antagonists) is unproven, so THC now sits as an option for nausea that resists first-line therapy ^{1Reference 1Smith LA et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →}.

3. Chronic & neuropathic pain

Across many RCTs and a 2026 Cochrane review, cannabis-based medicines produce a small reduction in chronic neuropathic pain, with sedation and dizziness common ^{6Reference 62026Systematic reviewCannabis-based medicines for chronic neuropathic pain in adults — Cochrane systematic reviewView study →}; the JAMA umbrella review rated the overall pain evidence moderate-quality ^{5Reference 5Whiting PF et al. · 2015Meta-analysisCannabinoids for Medical Use: A Systematic Review and Meta-analysisView study →}. THC is a genuine but modest analgesic, best considered for stubborn nerve pain rather than pain in general.

Gap: effect sizes are small and inconsistent, and in cancer pain specifically the evidence is largely null ^{5,6Reference 5Whiting PF et al. · 2015Meta-analysisCannabinoids for Medical Use: A Systematic Review and Meta-analysisView study →Reference 62026Systematic reviewCannabis-based medicines for chronic neuropathic pain in adults — Cochrane systematic reviewView study →}.

4. Appetite & cachexia

The appetite-stimulating “munchies” effect is real — THC drives appetite through CB1 receptors — and dronabinol supported appetite in HIV-associated wasting. In cancer cachexia, though, controlled trials are largely null: cannabinoids didn’t beat placebo or megestrol for appetite or weight ^{4Reference 4Mücke M et al. · 2018Meta-analysisSystematic review and meta-analysis of cannabinoids in palliative medicineView study →}.

Gap: the appetite effect is pharmacologically genuine but clinically unreliable where it’s most needed ^{4Reference 4Mücke M et al. · 2018Meta-analysisSystematic review and meta-analysis of cannabinoids in palliative medicineView study →}.

5. Glaucoma

A textbook case of a real effect that isn’t useful. THC does lower intraocular pressure, but only for about 3–4 hours per dose, which would demand near-continuous (and continuously intoxicating) dosing — which is why ophthalmology bodies don’t recommend it ^{8Reference 8Tomida I et al. · 2004ReviewCannabinoids and glaucoma — reviewView study →}.

Gap: the pressure-lowering is too short-lived to be practical, and no cannabis preparation is a recommended glaucoma therapy ^{8Reference 8Tomida I et al. · 2004ReviewCannabinoids and glaucoma — reviewView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
CB1 receptor partial agonism (CNS)	psychoactivity, appetite, anti-nausea, analgesia	nausea, appetite, pain
CB2 receptor agonism (immune tissue)	anti-inflammatory, immunomodulation	spasticity, inflammation
PPARγ activation	anti-inflammatory, neuroprotective, antitumour (preclinical)	broad

Pharmacokinetics

Route changes everything. Inhaled THC reaches the blood within minutes; taken orally, bioavailability is low and variable — roughly 6–20% — because of extensive first-pass metabolism, which also converts THC into 11-hydroxy-THC, a metabolite at least as psychoactive as THC itself, so eaten cannabis feels stronger and slower than the dose suggests ^{9Reference 9Grotenhermen F · 2003ReviewPharmacokinetics and Pharmacodynamics of Cannabinoids — review of human PKView study →}. THC is highly lipophilic, distributing into fat and clearing with a long, multi-phase terminal half-life, which is why it can be detected long after effects fade ^{9Reference 9Grotenhermen F · 2003ReviewPharmacokinetics and Pharmacodynamics of Cannabinoids — review of human PKView study →}.

Clinical trials

THC has a large trial footprint across nausea, spasticity, pain and appetite, much of it via the licensed pharmaceutical forms (dronabinol, nabilone, nabiximols) rather than whole plant.

Completed	Planned	Terminated	Preclinical
Many	Several	Some	Extensive

Last checked: July 2026.

Toxicity & Safety

Acute lethal toxicity is very low — there’s no established fatal dose — but THC’s risk profile follows from its CB1 activity. Acutely it impairs coordination, reaction time and judgement (impaired driving is one of its best-established harms) and can cause anxiety, paranoia or, at high doses, transient psychosis. With regular use it builds tolerance and dependence, and — the most important longer-term signal — heavier and higher-potency use is consistently associated with an increased risk of psychotic disorders, so it should be avoided by anyone with a personal or family history of psychosis or schizophrenia ^{10Reference 10Marconi A et al. · 2016Meta-analysisMeta-analysis of the Association Between the Level of Cannabis Use and Risk of PsychosisView study →}. THC also raises heart rate and can affect blood pressure, relevant in cardiovascular disease. Legal status varies widely (it remains federally Schedule I in the United States); the pharmaceutical form dronabinol is separately scheduled and prescription-only.

Pregnancy & lactation

Avoid. THC crosses the placenta and passes into breast milk, and prenatal cannabis exposure is associated with adverse neonatal outcomes including lower birth weight. It is not recommended during pregnancy or breastfeeding.

Dosage

The doses below are the studied pharmaceutical forms, not whole-flower use, and are not a recommendation — THC is psychoactive and, in most places, prescription-only or restricted. Whole-plant THC has no standardised dose; effects climb quickly with potency, so the practical rule for any THC-containing product is start low and go slow.

Application	Form	Dose (studied)	Source
Chemotherapy nausea	Dronabinol (synthetic THC)	~5 mg/m² per dose	1Reference 1Smith LA et al. · 2015Systematic reviewCannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic reviewView study →
MS spasticity	Nabiximols spray (2.7 mg THC + 2.5 mg CBD/spray)	self-titrated, up to ~12 sprays/day	2,3Reference 2Wade DT et al. · 2010Meta-analysisMeta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosisView study →Reference 3Filippini G et al. · 2022Systematic reviewCannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic reviewView study →

References

1. Smith LA, Azariah F, Lavender VT, et al. (2015). Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy — Cochrane systematic review. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/26561338/
2. Wade DT, Collin C, Stott C, Duncombe P (2010). Meta-analysis of the efficacy and safety of Sativex (nabiximols) on spasticity in people with multiple sclerosis. Multiple Sclerosis Journal. https://pubmed.ncbi.nlm.nih.gov/20558502/
3. Filippini G, Minozzi S, Borrelli F, et al. (2022). Cannabis and cannabinoids for symptomatic treatment for people with multiple sclerosis — Cochrane systematic review. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/35510826/
4. Mücke M, Weier M, Carter C, et al. (2018). Systematic review and meta-analysis of cannabinoids in palliative medicine. Journal of Cachexia, Sarcopenia and Muscle. https://pubmed.ncbi.nlm.nih.gov/29400010/
5. Whiting PF, Wolff RF, Deshpande S, et al. (2015). Cannabinoids for Medical Use: A Systematic Review and Meta-analysis. JAMA. https://pubmed.ncbi.nlm.nih.gov/26103030/
6. (2026). Cannabis-based medicines for chronic neuropathic pain in adults — Cochrane systematic review. Cochrane Database of Systematic Reviews. https://pubmed.ncbi.nlm.nih.gov/41548880/
7. Guzmán M, Duarte MJ, Blázquez C, et al. (2006). A pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme — clinical trial. British Journal of Cancer. https://pubmed.ncbi.nlm.nih.gov/16804518/
8. Tomida I, Pertwee RG, Azuara-Blanco A (2004). Cannabinoids and glaucoma — review. British Journal of Ophthalmology. https://pubmed.ncbi.nlm.nih.gov/15090428/
9. Grotenhermen F (2003). Pharmacokinetics and Pharmacodynamics of Cannabinoids — review of human PK. Clinical Pharmacokinetics. https://pubmed.ncbi.nlm.nih.gov/12648025/
10. Marconi A, Di Forti M, Lewis CM, et al. (2016). Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. Schizophrenia Bulletin. https://pubmed.ncbi.nlm.nih.gov/26884547/